0000000001269668

AUTHOR

Laura Gianserra

showing 3 related works from this author

Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1-4 in Italy

2018

AbstractNatural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mai…

Male0301 basic medicineSofosbuvirHepacivirusDrug Resistancelcsh:MedicineHepacivirusViral Nonstructural Proteinsmedicine.disease_causeGastroenterologyHepatitis C Virus; HCV resistance-testchemistry.chemical_compound0302 clinical medicineGenotypePrevalenceVirallcsh:ScienceHCV resistance-testMultidisciplinarybiologyHepatitis CMiddle AgedSettore MED/07 - Microbiologia e Microbiologia ClinicaHepatitis CItalyCohortHCVFemale030211 gastroenterology & hepatologymedicine.drugAdultmedicine.medical_specialtyHepatitis C VirusGenotypeHCV RASHepatitis C virus03 medical and health sciencesInternal medicineDrug Resistance ViralmedicineHumansAdult; Aged; Drug Resistance Viral; Female; Hepacivirus; Hepatitis C; Humans; Italy; Male; Middle Aged; Prevalence; Viral Nonstructural Proteins; GenotypeNS5ANS5BAgedbusiness.industrylcsh:RHepatitis C Virus HCV resistance-testbiology.organism_classificationmedicine.disease030104 developmental biologychemistrylcsh:Qbusiness
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Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

2017

Background Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results HCV-RNA kinetics was biphasic, reflecting …

Genetics and Molecular Biology (all)SimeprevirMaleHepacivirusHepacivirusPharmacologyBiochemistryStiffness0302 clinical medicineAnimal CellsMedicineAmino Acidslcsh:ScienceAlanineOrganic CompoundsLiver Diseases3. Good healthCirrhosisPhysical SciencesAdministrationInterferon030211 gastroenterology & hepatologyDrug Therapy CombinationCellular TypesOligopeptidesHumanOralMaterials ScienceGastroenterology and HepatologyMicrobiologyAntiviral Agents03 medical and health sciencesDrug TherapyHumansAgedKineticPharmacologyHepaciviruBiochemistry Genetics and Molecular Biology (all)Mathematical Modelinglcsh:RChemical CompoundsBiology and Life SciencesProteinsmedicine.diseasedigestive system diseasesAdministration Oral; Aged; Alanine Transaminase; Antiviral Agents; Drug Therapy Combination; Female; Hepacivirus; Hepatitis C; Humans; Interferons; Kinetics; Male; Middle Aged; Oligopeptides; RNA Viral; Ribavirin; Simeprevir; Sofosbuvir; Treatment Outcome; Viral Nonstructural Proteins; Biochemistry Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)030104 developmental biologyAgricultural and Biological Sciences (all)chemistryAliphatic Amino Acidslcsh:Q0301 basic medicineSofosbuvirlcsh:MedicineAdministration OralMedicine (all); Biochemistry Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)Viral Nonstructural ProteinsTelaprevirchemistry.chemical_compoundSimeprevirMedicine and Health SciencesViralMultidisciplinarybiologyAntimicrobialsMedicine (all)Simulation and ModelingDrugsAlanine TransaminaseHepatitis CMiddle AgedAntiviralsHepatitis CChemistryTreatment OutcomeLiverCombinationOligopeptideRNA ViralFemaleAnatomymedicine.drugResearch ArticleSettore MED/17 - Malattie InfettiveGeneral Science & TechnologyMaterial PropertiesResearch and Analysis MethodsMicrobial ControlVirologyRibavirinMechanical PropertiesNS5AAntiviral Agentbusiness.industryRibavirinHCV DAA ALTViral Nonstructural ProteinOrganic ChemistryCell Biologybiology.organism_classificationKineticsAlanine transaminaseAdministration Oral; Aged; Alanine Transaminase; Antiviral Agents; Drug Therapy Combination; Female; Hepacivirus; Hepatitis C; Humans; Interferons; Kinetics; Male; Middle Aged; Oligopeptides; RNA Viral; Ribavirin; Simeprevir; Sofosbuvir; Treatment Outcome; Viral Nonstructural Proteinsbiology.proteinHepatocytesRNAInterferonsSofosbuvirbusiness
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Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies

2017

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and w…

Male0301 basic medicinehepatitis C virusSustained Virologic ResponseSofosbuvirHepacivirusDrug ResistanceHepacivirusresistance-associated substitutionsViral Nonstructural ProteinsVARIANTSNS5Amedicine.disease_causeGastroenterologychemistry.chemical_compound0302 clinical medicineRecurrenceINFECTIONantiviral therapyMedicinehepatitis C viruViralTreatment FailureChronicantiviral therapy; direct-acting antivirals; hepatitis C virus; resistance test; resistance-associated substitutions; hepatologybiologyGENOTYPE 1virus diseasesMiddle Agedantiviral therapy; direct-acting antivirals; hepatitis C virus; resistance test; resistance-associated substitutionsSettore MED/07 - Microbiologia e Microbiologia ClinicaHepatitis CItalyCombinationInterferonDrug Therapy CombinationFemale030211 gastroenterology & hepatologyAuthor Keywords:antiviral therapyRIBAVIRINSequence AnalysisHumanmedicine.drugmedicine.medical_specialtyDaclatasvirGenotypeHepatitis C virusAntiviral AgentsLONG-TERM PERSISTENCEDACLATASVIR03 medical and health sciencesDrug Therapyantiviral therapy; direct-acting antivirals; hepatitis C virus; resistance test; resistance-associated substitutions; Aged; Antiviral Agents; Drug Resistance Viral; Drug Therapy Combination; Female; Genotype; Hepacivirus; Hepatitis C Chronic; Humans; Interferons; Italy; Male; Middle Aged; Mutation; Recurrence; Ribavirin; Sequence Analysis DNA; Sofosbuvir; Sustained Virologic Response; Treatment Failure; Viral Nonstructural Proteins; HepatologyTREATMENT-NAIVEInternal medicineDrug Resistance ViralRibavirinHumansNS5Aresistance testdirect-acting antiviralsAgedAntiviral Agentresistance-associated substitutiondirect-acting antiviralHepaciviruHepatologyresistance test KeyWords Plus:HEPATITIS-C VIRUSbusiness.industryRibavirinViral Nonstructural ProteinSequence Analysis DNADNAHepatitis C ChronicHepatologybiology.organism_classificationClinical trial030104 developmental biologySOFOSBUVIRchemistrySequence AnalysihepatologyMutationImmunologyInterferonsSofosbuvirbusiness
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